Ciliary entry of the kinesin-2 motor kif17 is regulated by importin-β2 and rangtp

ABSTRACT The biogenesis, maintenance and function of primary cilia are controlled through intraflagellar transport (IFT) driven by two kinesin-2 family members, the heterotrimeric

KIF3A/KIF3B/KAP complex and the homodimeric KIF17 motor1,2. How these motors and their cargoes gain access to the ciliary compartment is poorly understood. Here, we identify a ciliary

localization signal (CLS) in the KIF17 tail domain that is necessary and sufficient for ciliary targeting. Similarities between the CLS and classic nuclear localization signals (NLSs)

suggest that similar mechanisms regulate nuclear and ciliary import. We hypothesize that ciliary targeting of KIF17 is regulated by a ciliary-cytoplasmic gradient of the small GTPase Ran,

with high levels of GTP-bound Ran (RanGTP) in the cilium. Consistent with this, cytoplasmic expression of GTP-locked Ran(G19V) disrupts the gradient and abolishes ciliary entry of KIF17.

Furthermore, KIF17 interacts with the nuclear import protein importin-β2 in a manner dependent on the CLS and inhibited by RanGTP. We propose that Ran has a global role in regulating

cellular compartmentalization by controlling the shuttling of cytoplasmic proteins into nuclear and ciliary compartments. Access through your institution Buy or subscribe This is a preview

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ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE INTRAFLAGELLAR TRANSPORT

CYCLE Article 13 November 2024 REGULATION OF CILIARY HOMEOSTASIS BY INTRAFLAGELLAR TRANSPORT-INDEPENDENT KINESINS Article Open access 13 January 2024 TRAK ADAPTORS REGULATE THE RECRUITMENT

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Download references ACKNOWLEDGEMENTS This work was supported by NIH grants R01GM070862 and R01GM083254 (to K.J.V.), R01DC009606 (to J.R.M.), R01DK084725 (to B.M.), and T32GM007767 and

T32DC00011 (to P.M.J.). Work was also supported by NRSAs F32GM089034 (to J.F.D.) and F31DC009524 (to P.M.J.). H.L.K. is supported as a Barbour Fellow at the University of Michigan. pGEX-Ran

plasmids were a kind gift from Brian Burke (University of Florida) and rabbit anti-RanGTP antibody was a kind gift from Ian Macara (University of Virginia). AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA John F. Dishinger, Hooi Lynn Kee, Jennetta W. Hammond 

& Kristen J. Verhey * Department of Pharmacology, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA Paul M. Jenkins, Yen Nhu-Thi Truong & Jeffrey R. Martens *

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA Shuling Fan & Ben Margolis * Department of Biological Chemistry, University of

Michigan Medical School, Ann Arbor, 48109, Michigan, USA Ben Margolis * Department of Paediatrics and Communicable Disease, Division of Paediatric Nephrology, University of Michigan Medical

School, Ann Arbor, 48109, Michigan, USA Toby W. Hurd Authors * John F. Dishinger View author publications You can also search for this author inPubMed Google Scholar * Hooi Lynn Kee View

author publications You can also search for this author inPubMed Google Scholar * Paul M. Jenkins View author publications You can also search for this author inPubMed Google Scholar *

Shuling Fan View author publications You can also search for this author inPubMed Google Scholar * Toby W. Hurd View author publications You can also search for this author inPubMed Google

Scholar * Jennetta W. Hammond View author publications You can also search for this author inPubMed Google Scholar * Yen Nhu-Thi Truong View author publications You can also search for this

author inPubMed Google Scholar * Ben Margolis View author publications You can also search for this author inPubMed Google Scholar * Jeffrey R. Martens View author publications You can also

search for this author inPubMed Google Scholar * Kristen J. Verhey View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS J.F.D., H.L.K, P.M.J.,

S.F. and Y.N.T. performed experiments. J.F.D., H.L.K., P.M.J., J.R.M. and K.J.V. designed experiments. All authors contributed to helpful discussions shaping the aims of the project. J.F.D

and K.J.V. wrote the manuscript, with all authors providing detailed comments and suggestions. K.J.V. directed the project. CORRESPONDING AUTHOR Correspondence to Kristen J. Verhey. ETHICS

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and RanGTP. _Nat Cell Biol_ 12, 703–710 (2010). https://doi.org/10.1038/ncb2073 Download citation * Received: 16 March 2010 * Accepted: 04 May 2010 * Published: 06 June 2010 * Issue Date:

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